The mode (prophylaxis vs. episodic) and quantity of replacement of CFC are the most important determinant of long-term musculoskeletal outcome [24,25]. Studies from Sweden and the Netherlands proved that a near normal musculoskeletal function in severe PWH is due to prophylaxis. A Canadian study has shown that

prophylaxis started (even once a week) can reduce bleeding in such patients and that up to 40% of patients can continue this regimen later into childhood [6]. Most of these regimes are based on dosage of 25–40 IU/kg two to three times a week and require 3000–6000 IU/kg/yr of CFC and are deemed possible only in countries where CFC is available at 3–7 IU/capita [26,27]. Prophylaxis has therefore been mostly limited to the developed countries. In developing countries the range of availability

of CFC varies from Selleckchem GSK2118436 <0.1 to ∼3.0 IU per capita. Therefore CFC replacement therapy in these countries has remained predominantly episodic, or On Demand, thus for the treatment of bleeding only [28]. This is even the case for those who nowadays are able to get access Palbociclib nmr to 1000–2000 IU/kg/year. What outcome can patients in these countries expect? Unfortunately, data from several studies have shown that this mode of CFC replacement does not lead to adequate reduction in bleeding episodes so that most of these patients develop significant joint damage by the age of about 20 years with radiological joint scores of about 15–20 (Pettersson scale) [29]. The paramount question becomes whether alternative strategies for CFC replacement therapy can be considered, either found in developing countries with modest quantities of CFC, or in developed Grape seed extract countries. For the potential use of prophylaxis in developing countries, we will consider only those that are in the 1–2 IU/capita range or 1000–2000 IU/kg/year for individual

patients. Such centres should be able to offer prophylaxis at lower doses to PWH. If they start with 10 IU/kg twice a week, this will require a total of about 1000 IU/kg/year. This could then be increased to 10–15 IU/kg two to three times per week depending on patient responses and local access and availability of CFC. It would still require total doses less than 2000 IU/kg/year. Is there data to support such doses and schedules? Practice at Utrecht in the 1970s and 1980s showed that the use of CFC between 15–30 IU/kg resulted in significant reductions of joint bleeding (4). It has more recently been reported that such doses used as secondary prophylaxis in older children also reduced the incidence of joint bleedings significantly [30]. A prospective observation multi-center international study (HYPERLINK “”http://www.musfih.net”" http://www.musfih.